^(18)F标记BAY-588分子靶向肺腺癌预后标志物SLC2A1的计算模拟研究  

Predictive Biomarker SLC2A1 in Lung Adenocarcinoma Targeted by 18FBAY-588:A Computational Simulation Study

作　　者：李洋 高菲妃 原凌燕 杨琼[1,3] 刘家玮 邴志桐 LI Yang;GAO Feifei;YUAN Lingyan;YANG Qiong;LIU Jiawei;BING Zhitong(Institute of modern physics,Chinese Academy of Sciences,Lanzhou 730000,China;Life Sciences,University of Chinese Academy of Sciences,Beijing 100000,China;Advanced Energy Science and Technology Guangdong Laboratory,Huizhou 516000,Guangdong,China;School of Public Health,Lanzhou University,Lanzhou 730000,China)

机构地区：[1]中国科学院近代物理研究所,兰州730000 [2]中国科学院大学生命科学学院,北京100000 [3]先进能源科学与技术广东省实验室,广东惠州516000 [4]兰州大学公共卫生学院,兰州730000

出　　处：《原子核物理评论》2024年第4期1075-1084,共10页Nuclear Physics Review

基　　金：兰州市城关区科技计划项目(2020RCCX0033);东江实验室企业委托项目(HNO23XMHXJS)。

摘　　要：肺腺癌(Lung adenocarcinoma,LUAD)是一种发病率、致死率较高的疾病,目前针对肺腺癌的预后诊断的准确性和个体化水平有待进一步提高。基于生物信息学和正电子发射计算机断层成像技术(Positron Emission Tomography/Computed Tomography,PET/CT)建立预后模型和发掘靶向药物对该疾病的治疗具有重要意义。本研究采用Lasso-Cox算法对TCGA、GEO数据库中的肺腺癌转录组数据进行分析,筛选出与患者预后相关的基因,建立高性能的LUAD预后预测模型。该模型能够准确地区分高低风险患者,其一、三、五年生存率AUC值分别为0.821、0.693、0.701。基于该模型对ChEMBL数据库进行筛选,发现一种具有潜力的候选化合物BAY-588,对其进行18F放射性同位素标记的模拟计算,并揭示其可用于PET成像,为肺腺癌的诊断和治疗放射性药物的研发提供了科学证据。Lung adenocarcinoma(LUAD)is a disease with high morbidity and mortality rates,underscoring the need for enhanced accuracy and personalization in prognostic diagnostics.The integration of bioinformatics with positron emission tomography/computed tomography(PET/CT)presents substantial potential for the development of prognostic models and the identification of targeted therapeutics.In this study,we employed the Lasso-Cox algorithm to analyze LUAD transcriptomic data from the TCGA and GEO databases,successfully identifying prognosis-associated genes and constructing a high-performance prognostic prediction model.This model demonstrated robust stratification of high-and low-risk patients,achieving AUC values of 0.821,0.693,and 0.701 for 1-,3-,and 5-year survival rates,respectively.Subsequent virtual screening of the ChEMBL database using the model identified BAY-588 as a promising candidate compound.Computational simulations of 18F radiolabeling revealed its potential utility in PET imaging,providing scientific evidence for the development of theranostic radiopharmaceuticals targeting LUAD.

关 键 词：肺腺癌 预后 SLC2A1 分子对接 

分 类 号：R734.2[医药卫生—肿瘤] R979.12[医药卫生—临床医学]